From the fruits of
Fortunella crassifolia
and the peels of
Citrus junos
, two new limonoids, fortunellone and junosol were isolated together with three known compounds including nomilin. The chemical ...structures of the new compounds were elucidated based on chemical/physicochemical evidence. For fortunellone, the absolute configuration was established by comparison of experimental and predicted electronic circular dichroism (ECD) data. Fortunellon and nomilin significantly increased the number of dead cells on adriamycin (ADR)-treated human cervical cancer cells (HeLa). On the other hand, fortunellon and nomilin did not affects the number of dead cells alone. These results suggested that fortunellone and nomilin may have the potency as the chemotherapy enhancement agents.
Graphic abstract
Three new sesquiterpenes, valerianaterpenes I–III, and eight known compounds have been isolated from the methanol extract of the rhizomes and roots of
Valeriana fauriei
. The chemical structures of ...the three new sesquiterpenes were elucidated based on chemical and spectroscopic evidence. The absolute stereochemistry of valerianaterpene I was determined using X-ray crystallography. The cell death-inducing activity of isolated compounds alone or combination with Adriamycin (ADR) was observed by time-lapse cell imaging. Although the isolated compounds did not affect the number of mitotic entry cells and dead cells alone, kessyl glycol, kessyl glycol diacetate, and
iso
-teucladiol significantly increased the number of dead cells on ADR treated human cervical cancer cells. One of the mechanisms of cell death-inducing activity for the kessyl glycol acetate was suggested to be the inhibition of heat-shock protein 105 (Hsp105) expression level. This paper first deals with the naturally occurring compounds as Hsp105 inhibitor.
From the methanolic extract of the climbing stems and rhizomes of
Sinomenium acutum
, two new aporphine analogues, acutumalkaloids I and II, were isolated together with fifteen known compounds ...including lysicamine. The chemical structures of the isolated new compounds were elucidated based on chemical/physicochemical evidence such as NMR and MS spectra. For acutumalkaloids I and II, the absolute configurations were established by comparison of experimental and predicted electronic circular dichroism (ECD) data. We compared anti-proliferative activities of isolated compounds with reported naturally occurring Wnt/
β
-catenin pathway inhibitor, nuciferine. Among the isolated compounds, we found lysicamine have anti-proliferative activity against both of HT-29 human colon cancer cell line and its cancer stem cells (CSCs). The IC
50
values of lysicamine against non-CSCs and its CSCs were lower than that of nuciferine. In addition, the results of western blotting analysis suggested that lysicamine inhibited the expression of Wnt/
β
-catenin pathway target protein such as survivin. These results suggested that lysicamine show cytotoxic activity via inhibition of Wnt/
β
-catenin pathway.
Graphical abstract
We isolated the new sesquiterpenes, valerianaterpenes IV and V, and the new lignans valerianalignans I–III from the methanol extracts of the rhizomes and roots of Valeriana fauriei and elucidated ...their structures based on chemical and spectroscopic findings. The absolute configuration of valerianaterpene IV and valerianalignans I–III were established by comparing experimental and predicted electronic circular dichroism (ECD) data. Among the isolated compounds, valerianalignans I and II exerted anti-proliferative activity against human astrocytoma cells (U-251 MG) and their cancer stem cells (U-251 MG CSCs). Interestingly, valerianalignans I and II notably exerted anti-proliferative activities at lower concentrations against CSCs than non-CSCs, and the absolute configurations of these compounds affected their activities.
We isolated seven new iridoid glucosides (valerianairidoids I-VII;
-
,
,
,
, and
) and six known compounds from the methanol extract of the dried rhizomes and roots of
. Chemical and spectroscopic ...data were used to elucidate the chemical structures of the seven new iridoid glucosides, and their absolute configurations were determined by comparing their electronic circular dichroism (ECD) spectra with those determined experimentally. Aglycones
,
, and
, which were obtained by enzymatic hydrolysis of the isolated iridoid glucosides, exhibited anti-proliferative activities against cancer stem cells (CSCs) established by a sphere-formation assay using human breast cancer (MDA-MB-231) and human astrocytoma (U-251MG) cells. Interestingly, these iridoids selectively showed anti-proliferative activities against CSCs from MDA-MB-231 cells. These results suggest that the iridoids obtained in this study may have potency as a breast cancer treatment and as preventive agent via exterminating CSCs.
From the methanolic extract of the leaves of
Lansium domesticum
, three new onoceranoid-type triterpenoids, lansium acids X–XII and a new cycloartane-type triterpene, lansium acid XIII, were ...isolated. The chemical structures of the isolated new compounds were elucidated on the basis of chemical/physicochemical evidence. For new onoceranoid-type triterpenoids, the absolute configurations were established by comparison of experimental and predicted electronic circular dichroism (ECD) data. The isolated onoceranoid-type triterpenoids showed antimutagenic effects in the Ames assay against 3-amino-1,4-dimethyl-5
H
-pyrido4,3-
b
indole (Trp-P-1).
In cell transplantation therapy for spinal cord injury (SCI), grafted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) mainly differentiate into neurons, ...forming synapses in a process similar to neurodevelopment. In the developing nervous system, the activity of immature neurons has an important role in constructing and maintaining new synapses. Thus, we investigate how enhancing the activity of transplanted hiPSC-NS/PCs affects both the transplanted cells themselves and the host tissue. We find that chemogenetic stimulation of hiPSC-derived neural cells enhances cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhances the expression of synapse-related genes and proteins in surrounding host tissues and prevents atrophy of the injured spinal cord, thereby improving locomotor function. These findings provide a strategy for enhancing activity within the graft to improve the efficacy of cell transplantation therapy for SCI.
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•Human iPSC-derived neurospheres are transplanted into the injured spinal cord•Excitatory DREADD is lentivirally induced to the graft before the transplantation•The grafts are consecutively and selectively stimulated after the transplantation•Motor function improves because of enhanced synaptic activity by the stimulation
Kawai et al. transplant human iPSC-derived neural stem/progenitor cells in the sub-acute phase of rodent injured spinal cord, chemogenetically stimulating the graft repeatedly and selectively, and report improvements in motor functional recovery. Enhanced synaptic activity between the host and the graft is indicated to contribute to the functional recovery.
Background
In complete laparoscopic distal gastrectomy, the gastric resection line is difficult to determine due to a lack of tactile sensation. The use of intraoperative gastroscopy and ...intraoperative radiography has been reported, but the burden on personnel and technical complexity present impediments. In our department, based on lesion extent determined with preoperative gastroscopy, a fluorescent clip is used to mark the oral side of the lesion, which is resected after confirmation with a fluorescent laparoscopic system. In this study, we investigated the efficacy of fluorescent clip marking (FCM) in achieving an accurate resection line and reducing the operative time.
Methods
Fifty-six patients with gastric cancer who underwent complete laparoscopic distal gastrectomy from January 2018 to March 2021 were divided into two groups: the FCM group (
n
= 32) and the conventional metal clip marking and intraoperative gastroscopy (MCMG) group (
n
= 24). Short-term outcomes, including the resection margins, gastric resection time, and operative time, were compared and examined.
Results
The fluorescent clips were visible in all cases, and all stumps were negative according to permanent preparations. The operative times for FCM and MCMG were 350 (216–533) vs. 373.5 (258–651) min, respectively, with no significant difference (
p
= 0.316), while the gastric resection times were 636.5 (321–2572) vs. 1457.5 (843–4973) s, respectively, and were significantly shorter in the FCM group (
p
< 0.0001).
Conclusions
FCM shortened the gastric resection time and could possibly shorten the operative time. FCM is feasible and safe and can potentially be used as a tumor-marking agent to determine accurate surgical resection lines.
Clinical Trial Registration
Examination of Gastric Cancer, Research Ethics Committee of the Kawaguchi Municipal Medical Centre (Saitama, Japan), approval number: 2019-33.
https://kawaguchi-mmc.org/wp-content/uploads/clinicalresearch-r02.pdf
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