Nippon Veterinary and Life Science University

Peritoneal metastasis is the most lethal manifestation of gastric cancer, with a median survival of less than one year, highlighting the need for new therapeutic targets. Through an in vivo genome-wide CRISPR/Cas9 screen, we identified GRIA2, an AMPA-type glutamate receptor subunit, as a key driver of peritoneal metastasis. GRIA2 promotes gastric cancer cell migration, invasion, stemness, and adhesion to mesothelial cells in a glutamate-dependent manner. Mechanistically, glutamate activates GRIA2, enhancing its interaction with GSK-3β and inducing calcium influx, inhibiting GSK-3β kinase activity and stabilizing β-catenin, thereby activating the Wnt/β-catenin signaling pathway. Single-cell RNA sequencing revealed that cancer-associated fibroblasts are the primary source of glutamate in the peritoneal microenvironment, which establishes a paracrine axis that enhances GRIA2-driven metastasis. Pharmacological inhibition of AMPA receptors with NBQX and Selurampanel suppressed peritoneal metastasis in both cell line-derived and patient-derived organoid xenograft (PDOX) mouse models. In clinical analysis, GRIA2 expression in peritoneal metastases correlated with the levels of β-catenin and phosphorylated GSK-3β (serine 9), with high GRIA2 expression predicting poor prognosis. These findings suggest that GRIA2 is a novel therapeutic target, and AMPA receptor antagonists are promising agents for treating gastric cancer peritoneal metastasis.

This study aimed to investigate the neuroprotective effects of sweet potato petioles and leaves (PL), which are rich in polyphenols with antioxidant and anti-inflammatory properties, using a gerbil model of transient cerebral ischaemia. We also evaluated the preventive potential of continuous PL intake against ischaemic brain injury. Custom diets, formulated by adding 1% or 10% PL powder to MF standard diet, were provided ad libitum to gerbils after a 5-min bilateral common carotid artery occlusion for 7 days (post-ischaemia PL providing group). Diets were also provided from 7 days before to 7 days after the ischaemic episode (pre-ischaemia PL providing group, total 14 days). The number of viable neurons in the hippocampal CA1 region was assessed on postoperative Day 7. The number of viable neurons was significantly higher in both post- and pre-10% PL groups compared with that in the MF group (43.90±3.28 in MF, 66.55±6.60 in post 10% PL and 69.56±3.30 in pre 10% PL; p<0.01), although no significant differences were observed in the post- and pre-1% PL groups (55.49±3.19 in post 1% PL 47.27±2.61 in pre 1% PL). Moreover, comparison between the pre- and post-10% PL groups indicated that pre-ischaemic administration resulted in slightly higher number of viable neurons. Continuous intake of sweet potato PL may support the prevention and mitigation of neuronal damage in ischaemic events.

This immunohistochemical study evaluated the activity of primary sensory neurons in the vestibular ganglion in response to lowered barometric pressure (LBP) in mice to assess whether changes in barometric pressure were perceived by the vestibular system. Mice were anesthetized and exposed to three consecutive barometric pressure drops within the range of natural weather variations (-20hPa from the atmospheric pressure). Following anesthetization and paraformaldehyde perfusion 1-hour post-LBP exposure, activity-regulated cytoskeleton-associated protein (Arc) immunoreactive cells in the superior vestibular ganglion (SVG) and inferior vestibular ganglion (IVG) were counted bilaterally and compared with those of controls. In the positive control study, anesthetized mice were placed in the prone position and subjected to rotary motion (RM). The total number of Arc-positive neurons in the IVG, but not in the SVG, was significantly higher in LBP-exposed mice than in controls, regardless of sex. The total number of Arc-positive neurons in the SVG, but not in the IVG, was significantly higher in RM-stimulated mice than in controls. These data showed that primary sensory neurons in the IVG responded to LBP, strongly suggesting that changes in barometric pressure might be perceived by the saccule or posterior semicircular canal innervated by IVG neurons in mice.

The paper presents the findings on occurrence of cestode infection in wild carnivores during postmortem examination across different forest ranges in the Nilgiris district of Tamil Nadu, India over a period of sixteen months. A total of 37 wild carnivores comprising of seven dholes, four leopard cats, ten tigers and 16 leopards were examined from December 2023 to March 2025. Postmortem examination was conducted by the forest veterinary officer following standard procedures. The tapeworms were collected, labelled, processed as per standard procedures, identified and photographed. Out of the 37wild carnivores, 11 were found infected with cestodes (29.72%) which were identified as Taenia hydatigena morphologically. This comprised of one leopard cat (25%), two dholes (28.57%), five tigers(50%) and three leopards (18.75%). Out of the 11 infected animals, six were males (54.54%) and five were females (45.45%). Also, among the infected animals, one was below one year of age (9.09%) and 10 were above one year of age (90.90%).

This study investigated the effects of soy isoflavone yeast fermented extract (soyF) and soy isoflavone yeast unfermented extract (soyN) on rat ileal smooth muscle contraction. SoyF and soyN inhibited carbachol (CCh)- or KCl-induced contraction in a concentration-dependent manner; however, these effects were stronger for CCh-induced contraction than that for KCl, and the relaxation effect was stronger for soyF than for soyN. SoyF-induced relaxation was attenuated by 4-aminopyridine (4-AP), a Kv channel inhibitor, and iberiotoxin (IbTX), a calcium-activated potassium channel (BK channel) inhibitor. This relaxation was also decreased by 9-(tetrahydrofuran-2-yl)-9h-purin-6-amine (SQ22536) and 1H-[1, 2, 4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ). Moreover, simultaneous treatment involving SQ22536 with 4-AP or IbTX further restored soyF-induced inhibition compared with each single treatment, whereas simultaneous treatment with ODQ and 4-AP or IbTX did not restore soyF-induced inhibition. SoyF increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in ileal strips. In β-escin-permeabilized muscle, CCh, guanosine 5'-O(3-thiotriphosphate) (GTPγS), and phorbol-12,13-dibutyrate (PDBu)-enhanced Ca2+-induced contraction, but soyF suppressed this Ca2+ sensitization. In summary, yeast-fermented treatment increased soy isoflavone-induced inhibition of ileal smooth muscle contraction. These data suggest that soyF-induced relaxation was due to increasing cAMP and cGMP related to activating adenylate cyclase and guanylate cyclase. Moreover, it was demonstrated that soyF-induced relaxation is due to cell membrane hyperpolarization and inhibition of contractile proteins. Cell membrane hyperpolarization is probably mediated by the activation of Kv and BK channels via cGMP-related signals. Furthermore, the inhibitory effect on the contractile protein is due to Ca2+ desensitization, probably through suppression of the Rho kinase/myosin phosphatase targeting subunit (MYPT) and/or the PKC/CPI-17 pathway.

This study demonstrates that most common respiratory viruses, excluding influenza and DNA viruses, can replicate and produce infectious progeny for an average of up to 100 days in air-liquid interface (ALI) cultures of primary human respiratory epithelial cells without obvious innate immune responses. These findings imply that extended viral replication may occur in human hosts, potentially supported by the slow turnover of the respiratory epithelium. Notably, replication beyond 50-60 days was associated with the accumulation of genetic variations, suggesting a potential mechanism for the emergence of novel variants. To mitigate this risk, limiting transmission to within 50-60 days may be preferable. This issue is particularly relevant in immunocompromised individuals, where prolonged infection may promote viral evolution. Together, these findings provide insight into the replication dynamics of respiratory viruses in human tissue and highlight the importance of limiting long-term replication to prevent the emergence of new variants.

<title>Abstract</title> Gastric cancer (GC) remains a prevalent and lethal malignancy, with high rates of invasion and metastasis. Deiodinase 1 (DIO1) demonstrates the potential for tumor proliferation and invasion across various cancers, including GC. Herein, we aimed to investigate the role of DIO1 in tumor progression and its clinical significance in GC. In this study, we included 135 tumor microarray specimens from GC patients at Zhongshan Hospital, 329 GC patients from the <italic>Cancer Genome Atlas</italic>, and 300 GC patients from the <italic>Asian Cancer Research Group</italic>. Analysis of these three independent cohorts revealed that elevated DIO1 levels function as an independent adverse prognostic factor in GC. In vitro and in vivo studies manifested that DIO1 promotes GC cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through the WNT/β-catenin/Twist axis. Furthermore, DIO1 enhances CCL2 production, facilitating tumor-associated macrophage (TAM) chemotaxis. Functional assays confirmed that DIO1 knockdown suppresses GC progression while its overexpression exacerbates it. In conclusion, our findings indicated that DIO1 is a pivotal oncogene in GC, serving as a potential inferior prognostic marker and a promising therapeutic target for improving GC treatment outcomes.

The occurrence of Trichuris sp. nematodes in the caecum and colon of a free-ranging female gaur (Bos gaurus) observed during necropsy is reported. The body condition of the animal was thin with appreciable muscle wasting, sunken eye balls, rough hair coat, enlarged lymph nodes and pale mucous membrane. On necropsy, worms were found adhering to the mucosa of the caecum and colon. The worms were collected in 10% formalin, processed and identified as Trichuris sp. The worms were white in colour with whip-like anterior end, males were shorter than females. A total of 265 worms were recovered out of which 80 were male worms and 185 were female worms. The adult males were 30-55 mm long and 0.2-0.6 mm in width with a slender filiform anterior end comprising and a coiled posterior end. The adult females were 60-70 mm long and 0.3- 0.6 mm in width with a straight posterior end. It is however not probable that this infection could be one of the factors causing death of the animal.

Many strains of wild-type laboratory mice have been developed for studies in the life sciences, including skeletal muscle cell biology. Muscle regeneration capacity differs among wild-type mouse strains. However, few studies have focused on whether myogenic stem cells (satellite cells) are directly related to mouse strain-dependent myoregeneration gaps using in vitro culture models. In this study, we selected three major wild-type mouse strains, CD1 (outbred; Jcl:ICR [ICR]), C57BL/6NJcl (inbred; B6), and BALB/cAJcl (inbred; C), which are widely used in laboratory experiments. Initially, we compared myotube fusion capabilities using satellite cell-derived myoblasts. The results showed that cell cultures isolated from male ICR mice could not efficiently form myotubes owing to low expression levels of myogenic regulatory factors (e.g., MyoD, myogenin, myocyte enhancer factor [MEF] 2A, and MEF2C) compared with B6 and C mouse strains. Next, we compared the myofiber-type compositions of muscle tissues and cultured myotubes among male mice from each of the three strains. Although each muscle tissue used for satellite cell isolation similarly expressed fast-twitch myofiber markers in all mouse strains, male ICR-derived myoblasts formed abundant amounts of slow-type myotubes. By contrast, myotubes from male B6 and C mice expressed substantial levels of fast-twitch myofiber markers. We also performed a comparative experiment in female ICR, B6, and C mouse strains, similar to the male mouse experiments. The myogenic differentiation potencies of myoblasts and myofiber-type compositions of myotubes in female mouse strains were similar. Thus, male ICR-derived satellite cells (myoblasts) had low myogenic differentiation potential, which may be associated with the tendency slow-twitch myotube formation.