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Gastrointestinal cancers, which include a variety of esophageal and colorectal malignancies, present a global health challenge and require effective treatment strategies. In the evolving field of cancer immunotherapy, tissue-resident memory T cells (Trm cells) have emerged as important players in the immune response within nonlymphoid tissues. In this review, we summarize the characteristics and functions of Trm cells and discuss their profound implications for patient outcomes in gastrointestinal cancers. Positioned strategically in peripheral tissues, Trm cells have functions beyond immune surveillance, affecting tumor progression, prognosis, and response to immunotherapy. Studies indicate that Trm cells are prognostic markers and correlate positively with enhanced survival. Their presence in the tumor microenvironment has sparked interest in their therapeutic potential, particularly with respect to immune checkpoint inhibitors, which may improve cancer treatment. Understanding how Trm cells work will not only help to prevent cancer spread through effective treatment but will also contribute to disease prevention at early stages as well as vaccine development. The role of Trm cells goes beyond just cancer, and they have potential applications in infectious and autoimmune diseases. This review provides a thorough analysis of Trm cells in gastrointestinal cancers, which may lead to personalized and effective cancer therapies.

m6A RNA methylation, a predominant type of RNA modification, is involved in regulating mRNA splicing, stability, and translation as well as the interaction between nucleoproteins and noncoding RNAs. Recent studies have revealed that m6A RNA methylation plays a critical role in the self-to-non-self-recognition of immune cells against endogenous mutations in cancer and exogenous organism-related infections. As an epigenetic mechanism, m6A RNA modification induces immune cell signal transduction, which is altered in the tumor microenvironment, as detected in liquid biopsy. Furthermore, m6A RNA methylation-related inflammation is involved in the cellular response to viral infections, including the emerging severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Given the importance of the immune response in maintaining homeostasis in higher eukaryotes, m6A RNA methylation could be useful not only for the early detection of cancer but also for SARS-CoV-2 screening during a global pandemic.

Short non-coding RNAs, miRNAs, play roles in the control of cell growth and differentiation in cancer. Reportedly, the introduction of miRNAs could reduce the biologically malignant behavior of cancer cells, suggesting a possible use as therapeutic reagents. Given that the forced expression of several miRNAs, including miR-302, results in the cellular reprograming of human and mouse cells, which is similar to the effects of the transcription factors Oct4, Sox2, Klf4, and c-Myc, this suggests that the selective introduction of several miRNAs will be able to achieve anti-cancer effects at the epigenetic and metabolic levels. In this review article, we bring together the recent advances made in studies of microRNA-based therapeutic approaches to therapy-resistant cancers, especially in gastrointestinal organs.

An international project on the human genome revealed that various RNAs (e.g., messenger RNAs, microRNAs, and long noncoding RNAs [lncRNAs] and their subclass circular RNA [circRNA)) are involved in the pathogenesis of different human diseases, including cancer. Recent studies have highlighted the critical roles of lncRNAs and circRNA in pancreatic ductal adenocarcinoma (PDAC), especially in the epithelial–mesenchymal transition, a phenomenon regulating cancer metastasis. Growing research in this field has indicated that the tertiary structure of lncRNAs supposedly regulates biological function via RNA–RNA or RNA–protein associations, aiding early diagnosis and therapy selection for various diseases, including cancer. Here we describe the emerging roles of ncRNAs in PDAC and highlight how these ncRNAs can be used to detect and control this intractable cancer.

Background: To clarify the changes in the echo intensity (EI) in the prefemoral fat pad (PFP) and identify the relationship between the PFP and clinical features of knee osteoarthritis (OA). Methods: Twenty-six women with knee OA (mean age: 76 years) and 17 healthy women (mean age: 73 years) were enrolled. The Kellgren and Lawrence grading scale was used for the radiographic evaluation of knee OA. The EI of the PFP was measured as grayscale values. The change ratio of the anteroposterior PFP length during quadriceps contraction was measured. Knee range of motion and pain (100-mm visual analog scale) were evaluated. Results: The EI was significantly higher in the OA group than in the healthy group (P < 0.001). The change ratio of the PFP in the OA group was significantly lower than that in the healthy group (P < 0.001). The ranges of knee flexion and extension were correlated with the EI of the PFP (both P < 0.01) and the change ratio of the PFP (both P < 0.01). There was no significant correlation observed with knee pain. Conclusion: Hyperechoic changes and a decreased change ratio of the PFP were observed in the patients with knee OA. High EI and decreased morphological PFP changes were associated with decreased ranges of motion.

Pancreatic ductal adenocarcinoma (PDAC) is caused by genetic mutations in four genes: KRAS proto-oncogene and GTPase (KRAS), tumor protein P53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), and mothers against decapentaplegic homolog 4 (SMAD4), also called the big 4. The changes in tumors are very complex, making their characterization in the early stages challenging. Therefore, the development of innovative therapeutic approaches is desirable. The key to overcoming PDAC is diagnosing it in the early stages. Therefore, recent studies have investigated the multifaced characteristics of PDAC, which includes cancer cell metabolism, mesenchymal cells including cancer-associated fibroblasts and immune cells, and metagenomics, which extend to characterize various biomolecules including RNAs and volatile organic compounds. Various alterations in the KRAS-dependent as well as KRAS-independent pathways are involved in the refractoriness of PDAC. The optimal combination of these new technologies is expected to help treat intractable pancreatic cancer.

Background: In normal knees, quadriceps contraction changes the shape of the prefemoral fat pad (PFP). However, in persons with knee osteoarthritis (OA), the functional or morphological changes of the PFP are unclear. This study aimed to clarify the morphological changes in the PFP in individuals with knee OA through ultrasonography. Materials and Methods: Participants were divided into the OA (36 knees; mean age, 74 years), elderly (31 knees; mean age, 70 years), and young (26 knees; mean age, 21 years) groups. The anteroposterior (AP) length of the PFP before and during isometric quadriceps contraction at 0°, 30°, 60°, and 90° knee flexion was measured ultrasonographically. The difference between the maximum and minimum length values, change in length, was also measured. These parameters were compared among the three groups. In the OA group, correlations between the parameters and clinical features (knee pain; visual analog scale, knee range of motion [ROM], Kellgren and Lawrence (K/L) grade, and intercondylar distance) were examined by Spearman and Pearson's correlation coefficient tests. Results: The AP lengths of the PFP before contraction were significantly lower in the OA group than in elderly group and young group at 30° (6.9 ± 2.5 vs. 12.0 ± 3.6 or 11.1 ± 2.7 mm, respectively; in order P = 0.014, P = 0.006) and 60° (6.5 ± 2.0 vs. 9.7 ± 2.5 or 9.1 ± 2.7 mm, respectively; both P < 0.001). The AP lengths of the PFP during contraction were significantly lower in the OA group than in elderly group and young group at 0° (6.7 ± 2.3 vs. 8.8 ± 3.7 or 9.1 ± 1.6 mm, respectively; both P < 0.001), 30° (7.9 ± 2.6 vs. 12.9 ± 3.7 or 13.0 ± 2.6 mm, respectively; both P < 0.001), and 60° (7.1 ± 2.5 vs. 13.5 ± 2.6 or 13.6 ± 3.0 mm, respectively; both P < 0.001). The change in length before maximum isometric quadriceps contraction was significantly lower in the knee OA group than in both elderly and young groups (3.3 ± 1.9 vs. 8.4 ± 2.5 or 6.8 ± 3.0 mm, respectively; both P < 0.001). The change in length during contraction was also significantly lower in the knee OA group than in both the elderly and young groups (3.9 ± 2.3 vs. 8.7 ± 2.3 or 8.9 ± 2.0 mm, respectively; both P < 0.001). In the OA group, change in length during contraction was significantly associated with knee pain (r = −0.476, P = 0.007), knee ROM (r = 0.388, P = 0.019), and Kellgren and Lawrence grade (r = −0.357, P = 0.045). Conclusions: In knee OA, movement of PFP was decreased more than healthy participants. In the knee OA group, the decrease of the morphological change of the PFP showed the relationship between VAS score, knee extension ROM, intercondylar distance (ICD), and K/L grade. An evaluation to the PFP may be required in individuals with knee OA.

Acetylcholine (ACh) is secreted from cholinergic neurons in the basal forebrain to regions throughout the cerebral cortex, including the primary visual cortex (V1), and influences neuronal activities across all six layers via a form of diffuse extrasynaptic modulation termed volume transmission. To understand this effect in V1, we performed extracellular multi-point recordings of neuronal responses to drifting sinusoidal grating stimuli from the cortical layers of V1 in anesthetized rats and examined the modulatory effects of topically administered ACh. ACh facilitated or suppressed the visual responses of individual cells with a laminar bias: response suppression prevailed in layers 2/3, whereas response facilitation prevailed in layer 5. ACh effects on the stimulus contrast-response function showed that ACh changes the response gain upward or downward in facilitated or suppressed cells, respectively. Next, ACh effects on the signal-to-noise (S/N) ratio and the grating-phase information were tested. The grating-phase information was calculated as the F1/F0 ratio, which represents the amount of temporal response modulation at the fundamental frequency (F1) of a drifting grating relative to the mean evoked response (F0). In facilitated cells, ACh improved the S/N ratio, while in suppressed cells it enhanced the F1/F0 ratio without any concurrent reduction in the S/N ratio. These effects were predominantly observed in regular-spiking cells, but not in fast-spiking cells. Electrophysiological and histological findings suggest that ACh promotes the signaling of grating-phase information to higher-order areas by a suppressive effect on supragranular layers and enhances feedback signals with a high S/N ratio to subcortical areas by a facilitatory effect on infragranular layers. Thus, ACh distinctly and finely controls visual information processing in a manner that is specific for the modulation and cell type and is also laminar dependent.

RN7SL1 (RNA component of signal recognition particle 7SL1), a component of the signal recognition particle, is a non-coding RNA possessing a small ORF (smORF). However, whether it is translated into peptides is unknown. Here, we generated the RN7SL1-Green Fluorescent Protein (GFP) gene, in which the smORF of RN7SL1 was replaced by GFP, introduced it into 293T cells, and observed cells emitting GFP fluorescence. Furthermore, RNA-seq of GFP-positive cells revealed that they were in an oncogenic state, suggesting that RN7SL1 smORF may be translated under special conditions. [ABSTRACT FROM AUTHOR]

Pancreatic cancer stem cells (CSCs) play a key role in the initiation and progression of pancreatic adenocarcinoma (PDAC). CSCs are responsible for resistance to chemotherapy and radiation, and for cancer metastasis. Recent studies have indicated that RNA methylation, a type of RNA modification, predominantly occurring as m6A methylation, plays an important role in controlling the stemness of cancer cells, therapeutic resistance against chemotherapy and radiation therapy, and their overall relevance to a patient's prognosis. CSCs regulate various behaviors of cancer through cell-cell communication by secreting factors, through their receptors, and through signal transduction. Recent studies have shown that RNA methylation is involved in the biology of the heterogeneity of PDAC. The present review provides an update on the current understanding of RNA modification-based therapeutic targets against deleterious PDAC. Several key pathways and agents that can specifically target CSCs have been identified, thus providing novel insights into the early diagnosis and efficient treatment of PDAC. [ABSTRACT FROM AUTHOR]

In the primary visual cortex (V1), a neuronal response to stimulation of the classical receptive field (CRF) is predominantly suppressed by a stimulus presented outside the CRF (extraclassical receptive field, ECRF), a phenomenon referred to as ECRF suppression. To elucidate the neuronal mechanisms and origin of ECRF suppression in V1 of anesthetized cats, we examined the temporal properties of the spatial extent and orientation specificity of ECRF suppression in V1 and the lateral geniculate nucleus (LGN), using stationary-flashed sinusoidal grating. In V1, we found three components of ECRF suppression: 1) local and fast, 2) global and fast, and 3) global and late. The local and fast component, which resulted from within 2° of the boundary of the CRF, started no more than 10 ms after the onset of the CRF response and exhibited low specificity for the orientation of the ECRF stimulus. These spatiotemporal properties corresponded to those of geniculate ECRF suppression, suggesting that the local and fast component of V1 is inherited from the LGN. In contrast, the two global components showed rather large spatial extents ∼5° from the CRF boundary and high specificity for orientation, suggesting that their possible origin is the cortex, not the LGN. Correspondingly, the local component was observed in all neurons of the thalamocortical recipient layer, while the global component was biased toward other layers. Therefore, we conclude that both subcortical and cortical mechanisms with different spatiotemporal properties are involved in ECRF suppression. [ABSTRACT FROM AUTHOR]

Cells in the rat barrel cortex exhibit stimulus-specific response properties. To understand the network mechanism of direction selectivity in response to facial whisker deflection, we examined direction selectivity of neuronal responses to single- and multiwhisker stimulations. In the case of regular-spiking units, i.e., putative excitatory cells, direction preferences were quite similar between responses to single-whisker stimulation of the principal and adjacent whiskers. In multiwhisker stimulation at short (≤5 ms) interstimulus intervals (ISIs), response facilitation was evoked only when the whiskers were deflected to the preferred direction of the response to the single whisker stimulation. These results suggest that there are neuronal networks among cells with different whisker preferences but with a common direction preference that could be the neuronal basis of the direction-selective facilitation of the response to multiwhisker stimulation. In contrast, multiwhisker stimulation at long (≥6 ms) ISIs caused non–direction-selective suppression of the response to the second stimulus. In the case of fast-spiking units, i.e., putative inhibitory cells, poor direction selectivity was exhibited. Thus stimulus direction is represented as the direction-selective responses to the single- and multiwhisker stimulations of putative excitatory cells rather than those of putative inhibitory cells. [ABSTRACT FROM AUTHOR]

Novel rhodium(i) complexes with N-heterocyclic carbenes bearing a 2,3,4,5-tetraphenylphenyl and its higher dendritic frameworks were synthesized and the complexes were used as catalysts in rhodium-catalyzed hydrosilylation of α,β-unsaturated ketones to show high 1,4-adduct selectivity. [ABSTRACT FROM AUTHOR]