Development of light-induced disruptive liposomes (LiDL) as a photoswitchable carrier for intracellular substance delivery

Light-driven inward proton pump rhodopsin RmXeR was embedded in pH-sensitive liposomes. Substance release from the proteoliposomes was observed following light illumination both in vitro and in cells, indicating the successful production of light-induced disruptive liposomes (LiDL). Thus, LiDL is a photoswitchable carrier utilized for intracellular substance delivery

脂肪由来間葉系幹細胞からインスリン産生細胞への分化誘導に際しての皮下および腹腔内脂肪の特性の差異に関する研究

The aim of this study was to investigate the characteristics of insulin producing cells (IPCs) differentiated from adipose-tissue derived stem cells (ADSCs) isolated from human subcutaneous and visceral adipose tissues and identify ADSCs suitable for differentiation into efficient and functional IPCs. Subcutaneous and visceral adipose tissues collected from four (4) patients who underwent digestive surgeries at The Tokushima University (000035546) were included in this study. The insulin secretion of the generated IPCs was investigated using surface markers by: fluorescence activated cell sorting (FACS) analysis; cytokine release; proliferation ability of ADSCs; in vitro (glucose-stimulated insulin secretion: (GSIS) test/in vivo (transplantation into streptozotocin-induced diabetic nude mice). The less fat-related inflammatory cytokines secretions were observed (P < 0.05), and the proliferation ability was higher in the subcutaneous ADSCs (P < 0.05). Insulin expression and GISI were higher in the subcutaneous IPCs (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of all mice that received IPCs from subcutaneous fat tissue converted into normo-glycaemia in thirty (30) days post-transplantation (4/4,100%). Transplanted IPCs were stained using anti-insulin and anti-human leukocyte antigen antibodies. The IPCs generated from the ADSCs freshly isolated from the human fat tissue had sufficient insulin secreting ability in vitro and in vivo

亜鉛イオン濃度変化は脂肪由来幹細胞から作成するインスリン産生細胞の成熟を反映する

The generation of insulin-producing cells (IPCs) from pluripotent stem cells could be a breakthrough treatment for type 1 diabetes. However, development of new techniques is needed to exclude immature cells for clinical application. Dithizone staining is used to evaluate IPCs by detecting zinc. We hypothesised that zinc ion (Zn2+) dynamics reflect the IPC maturation status. Human adipose-derived stem cells were differentiated into IPCs by our two-step protocol using two-dimensional (2D) or 3D culture. The stimulation indexes of 2D -and 3D-cultured IPCs on day 21 were 1.21 and 3.64 (P < 0.05), respectively. The 3D-cultured IPCs were stained with dithizone during culture, and its intensity calculated by ImageJ reached the peak on day 17 (P < 0.05). Blood glucose levels of streptozotocin-induced diabetic nude mice were normalised (4/4,100%) after transplantation of 96 3D-cultured IPCs. Zn2+ concentration changes in the medium of 3D cultures had a negative value in the early period and a large positive value in the latter period. This study suggests that Zn2+ dynamics based on our observations and staining of zinc transporters have critical roles in the differentiation of IPCs, and that their measurement might be useful to evaluate IPC maturation as a non-destructive method

HIF-1α expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis

Background: The role of hypoxia-inducible factor-1α (HIF-1α) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1α expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). Methods: Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1α expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1α expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. Results: Activated HSCs induced HIF-1α mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1α expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1α expression in primary CRC. However, HIF-1α expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1α positive expression in liver metastasis had poor prognosis. Conclusion: HIF-1α expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells

EGCG HINDERS METABOLIC COUPLING BETWEEN CANCER AND CAFs

In recent times, researchers working on tumor metabolism have paid increasing attention to the tumor microenvironment. Emerging evidence has confirmed that epigenetic modifications of cancer‑associated fibroblasts (CAFs) alters the characteristics of glucose metabolism to achieve a symbiotic relationship with the cancer cells. Epigallocatechin‑3‑gallate (EGCG) exerts anti‑tumor effects via a variety of mechanisms, although the underlying mechanism that accounts for the effects of EGCG on glucose metabolic alterations of CAFs have yet to be elucidated. In the present study, through co‑culture with colorectal cancer (CRC) cells, human intestinal fibroblasts were transformed into CAFs, and exhibited enhanced aerobic glycolysis. Induced CAFs were able to enhance the proliferation, migration and invasion of CRC cells in vitro. EGCG treatment led to direct inhibition of the proliferation and migration of CRC cells; furthermore, EGCG treatment of CAFs suppressed their tumor‑promoting capabilities by inhibiting their glycolytic activity. Blocking the lactic acid efflux of CAFs with a monocarboxylate transporter 4 (MCT4) inhibitor or through silencing MCT4 could also suppress their tumor‑promoting capabilities, indicating that lactate fulfills an important role in the metabolic coupling that occurs between CAFs and cancer cells. Taken together, the results of the present study showed that EGCG targeting of the metabolism of tumor stromal cells provided a safe and effective strategy of anti‑cancer therapy

Development of an Autonomous Vehicle Equipped with a Broadband Ultrasonic Sensor (Thermophone) for Engineering Verification of the Bats Jamming Avoidance Behavior

The 11th International Symposium on Adaptive Motion of Animals and Machines. Kobe University, Japan. 2023-06-06/09. Adaptive Motion of Animals and Machines Organizing Committee.Poster Session P3

The inhibitory effect of TU-100 on hepatic stellate cell activation in the tumor microenvironment

Introduction: The tumor microenvironment is involved in acquiring tumor malignancies of colorectal liver metastasis (CRLM). We have reported that TU-100 (Daikenchuto) suppresses hepatic stellate cell (HSC) activation in obstructive jaundice. In this study, we report new findings as the direct and indirect inhibitory effects of TU-100 on cancer cell growth through the suppression of HSC activation. Materials and Methods: The HSCs (LX2) were cultured in colon cancer cells (HCT116 and HT29)-conditioned medium (CM) with or without TU-100 treatment (90, 270, 900 μg/ml). Activated HSCs (aHSCs) were detected by α-SMA and IL-6 mRNA expressions and cytokine arrays of HSC’s culture supernatants. Cancer cell growth was analyzed for proliferation and migration ability, compared with TU-100 treatment. To investigate the direct anti-tumor effect of TU-100, cancer cells were cultured in the presence of aHSC-CM and TU-100 (90, 270, 900) or aHSC-CM alone, and assessed autophagosomes, conversion to LC3-II protein, and Beclin-1 mRNA expression. Results: Colon cancer-CM significantly increased α-SMA and IL-6 mRNA expressions of aHSC. α-SMA and IL-6 mRNA expressions of aHSC, and IL-6 secretions from aHSCs were significantly decreased with TU-100 (270, 900) treatment, compared to colon cancer-CM alone. Compared with normal culture medium, aHSC-CM led to a significantly increased cell number and modified HSC-CM (TU-100; 270, 900) significantly suppressed cancer cell growth and migration. TU-100 (900) treatment induced autophagy and significantly promoted the autophagic cell death. Conclusions: TU-100 inhibited colon cancer cell malignant potential by both suppressing HSC activation and inducing directly autophagy of cancer cells

Impact of frailty in elderly GC patients

Background : Frailty plays a crucial role in cancer patients who have received surgery in this recent aging society. We aimed to investigate frailty as a prognostic factor in elderly gastric cancer (GC) patients who underwent curative gastrectomy. Methods : We analyzed 86 elderly (over 75 years old) GC patients who underwent curative gastrectomy. Patients were assigned to two groups ; frailty group (n = 29) and no-frailty group (n = 57). Clinicopathological values were compared between the two groups. Results : The OS rate of the frailty group was significantly poorer than that of the no-frailty group (5-yr OS rate ; frailty group 52.49% vs. no-frailty group 74.87%, p < 0.05). Multivariate analysis of the OS showed that frailty tended to be significant prognostic factor (p = 0.09). The DFS rate of the frailty group was significantly poorer than that of the no-frailty group (5-yr DFS rate ; frailty group 42.30% vs. no-frailty group 71.55%, p < 0.05). Multivariate analysis of the DFS showed that frailty tended to be significant prognostic factor (p = 0.14). Conclusion : We identified the clinical impact of frailty prognostic factor for elderly GC patients who underwent gastrectomy

Electrode montage for transcranial direct current stimulation governs its effect on symptoms and functionality in schizophrenia

BackgroundsPatients with schizophrenia suffer from cognitive impairment that worsens real-world functional outcomes. We previously reported that multi-session transcranial direct current stimulation (tDCS) delivered to the left dorsolateral prefrontal cortex (DLPFC) improved daily living skills, while stimulation on the left superior temporal sulcus (STS) enhanced performance on a test of social cognition in these patients. To examine the region-dependent influence of tDCS on daily-living skills, neurocognition, and psychotic symptoms, this study compared effects of anodal stimulation targeting either of these two brain areas in patients with schizophrenia.MethodsData were collected from open-label, single-arm trials with anodal electrodes placed over the left DLPFC (N = 28) or STS (N = 15). Daily-living skills, neurocognition, and psychotic symptoms were measured with the UCSD performance-based skills assessment-brief (UPSA-B), Brief Assessment of Cognition in Schizophrenia (BACS), and Positive and Negative Syndrome Scale (PANSS), respectively. After baseline evaluation, tDCS (2 mA × 20 min) were delivered two times per day for 5 consecutive days. One month after the final stimulation, clinical assessments were repeated.ResultsPerformance on the UPSA-B was significantly improved in patients who received anodal tDCS at the left DLPFC (d = 0.70, p &lt; 0.001), while this effect was absent in patients with anodal electrodes placed on the left STS (d = 0.02, p = 0.939). Significant improvement was also observed for scores on the BACS with anodal tDCS delivered to the DLPFC (d = 0.49, p &lt; 0.001); however, such neurocognitive enhancement was absent when the STS was stimulated (d = 0.05, p = 0.646). Both methods of anodal stimulation showed a significant improvement of General Psychopathology scores on the PANSS (DLPFC, d = 0.50, p = 0.027; STS, d = 0.44, p = 0.001).ConclusionThese results indicate the importance of selecting brain regions as a target for tDCS according to clinical features of individual patients. Anodal stimulation of the left DLPFC may be advantageous in improving higher level functional outcomes in patients with schizophrenia.Trial registrationThese studies were registered within the University hospital Medical Information Network Clinical Trials Registry [(24), UMIN000015953], and the Japan Registry of Clinical Trials [(28), jRCTs032180026]

Understanding controls on biotic assemblages and ecological status in Zambian rivers for the development of sustainable monitoring protocols

We search for galaxies with a strong Balmer break (Balmer Break Galaxies; BBGs) at $z \sim 6$ over a 0.41 deg$^2$ effective area in the COSMOS field. Based on rich imaging data, including data obtained with the Atacama Large Millimeter/submillimeter Array (ALMA), three candidates are identified by their extremely red $K - [3.6]$ colors as well as by non-detection in X-ray, optical, far-infrared (FIR), and radio bands. The non-detection in the deep ALMA observations suggests that they are not dusty galaxies but BBGs at $z \sim 6$, although contamination from Active Galactic Nuclei (AGNs) at $z \sim 0$ cannot be completely ruled out for the moment. Our spectral energy distribution (SED) analyses reveal that the BBG candidates at $z \sim 6$ have stellar masses of $\approx 5 \times 10^{10} M_{\odot}$ dominated by old stellar populations with ages of $\gtrsim 700$ Myr. Assuming that all the three candidates are real BBGs at $z \sim 6$, we estimate the stellar mass density (SMD) to be $2.4^{+2.3}_{-1.3} \times 10^{4} M_{\odot}$ Mpc$^{-3}$. This is consistent with an extrapolation from the lower redshift measurements. The onset of star formation in the three BBG candidates is expected to be several hundred million years before the observed epoch of $z \sim 6$. We estimate the star-formation rate density (SFRD) contributed by progenitors of the BBGs to be 2.4 -- 12 $\times 10^{-5} M_{\odot}$ yr$^{-1}$Mpc$^{-3}$ at $z > 14$ (99.7\% confidence range). Our result suggests a smooth evolution of the SFRD beyond $z = 8$.Comment: 29 pages, 16 figures, 4 tables, accepted for publication in Ap